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The use of tobacco products remains the major preventable cause of cardiovascular disease and mortality. Although much progress has been made in reducing the prevalence of smoking, new opportunities to regulate tobacco products and the recent introduction of e-cigarettes in the market have radically redefined the tobacco landscape. These developments have heightened the need for a more in-depth understanding of the effects of tobacco products on heart disease, and for identifying which components of tobacco products cause cardiovascular damage and which biomarkers and subclinical measures of cardiovascular disease are most reflective of tobacco-induced injury. This understanding is essential not only for developing new regulatory policies, but also for evaluating disease risk that might be associated with the use of new devices such as e-cigarettes. Because the concentration of several harmful and potentially harmful constituents present in cigarette smoke is decreased in e-cigarettes, it has been suggested that the use of e-cigarettes could significantly lessen the burden of cardiovascular disease. E-cigarettes have also been claimed to promote smoking cessation. However, the extent of residual risk associated with carbonyls, particulate matter, nicotine, flavors, and other constituents of e-cigarettes is unclear, and the efficacy of e-cigarettes as cessation devices remains uncertain. Widespread acceptance of these devices could renormalize the use of tobacco products and recruit a new generation of users to nicotine addiction. Therefore, further toxicological, clinical, economic, and marketing research is required to chart a clear, evidence-based pathway for alleviating the cardiovascular disease burden of tobacco products.

Even after decades of aggressive antismoking campaigns, after banning cigarettes from most public places, after social denormalization of tobacco use, and after the accumulation of extensive evidence linking tobacco products to early mortality, smoking continues to be the leading cause of preventable death worldwide, killing >480 000 American every year, accounting for ≈5 million premature deaths worldwide, and costing >$300 billion in healthcare costs and lost productivity in the United States alone.1 More than 40 million American still smoke cigarettes, and globally, the number of smokers exceeds 1 billion. Although it is well known that smoking increases the risk of many diseases, cardiovascular disease is the major cause of premature mortality in smokers. The number of cardiovascular deaths because of smoking (1.69 million) far exceeds smoking-related deaths from cancer (0.97 million) and pulmonary disease (0.85 million).2 Yet, despite this high disease burden, we know little about the mechanisms by which smoking affects cardiovascular health. We do not know how smoking accelerates atherogenesis, promotes negative tissue remodeling, or triggers plaque rupture. And we have not yet identified specific cardiovascular targets of smoking or individual constituents of tobacco smoke, responsible for cardiovascular injury in smokers.

Many consider such ignorance inconsequential. Smoking, they argue, is an entirely preventable, unhealthy choice, and therefore, our efforts should be directed at cessation rather than studying the harmful effects of smoking. However, for many long-term smokers, smoking is not a choice but a compulsion of their nicotine addiction. Moreover, several risk factors such as hypertension, dyslipidemia, and obesity are linked to unhealthy lifestyle choices such as excessive salt intake, physical inactivity, or overeating. Yet, we devote significant resources to studying these largely preventable risk factors. Smoking merits similar consideration. Certainly, a phenomenon that affects the cardiovascular health of >1 billion individuals deserves our utmost attention and interest.

The current exclusion of smoking from in-depth scientific study may be an unintended consequence of our success in denormalizing smoking. Because we have succeeded in removing smoking from public view and discourse (expect for regulatory and cessation-promoting purposes), it may have also contributed to the removal of smoking from serious scientific consideration. Few major funding agency support a large portfolio of smoking-related cardiovascular research and the little extant support there is, is far outweighed by the extent and the scope of the problem. Most clinicians and public health advocates, experiencing little smoking in their immediate environment, have paradoxically accepted smoking as an inevitable consequence of an abnormal behavior of derelict individuals at the fringe of an otherwise enlightened society of individuals with admirable self-control. But in the past few years, the tobacco landscape has changed completely. New opportunities and challenges have emerged that could radically redefine the relationship between tobacco use and heart disease, and our perception of smoking and its place in society.

This new scenario was inaugurated with the passing of the Family Smoking Prevention and Control Act in 2009, which gave US Food and Drug Administration the authority to regulate the manufacture, distribution, and marketing of tobacco products. The Act is an attempt to prevent and reduce tobacco use in young people and to prohibit false and misleading labeling and advertising of tobacco products. Importantly, the bill allows provisions to regulate nicotine yields of tobacco products as well as the construction, ingredients, additives, constituents, components, and properties of these products. This Act led to the creation of the US Food and Drug Administration Center for Tobacco Products to set performance standards, review premarket applications for new and modified risk tobacco products, and establish and enforce advertising and promotion restrictions. The Center for Tobacco Products also funds research on topics that are important to the future of tobacco regulation. But many challenges remain. Because of our previous neglect of smoking research, we do not know which constituents, ingredients, and additives contribute to the toxicity of tobacco products. As a result, we are not sure what to regulate. Moreover, because we do not know which subclinical processes contribute to the development of tobacco-induced cardiovascular disease or which biomarkers of exposure or harm are most informative of tobacco-induced cardiovascular injury, we are not even sure how, without waiting for mortality data, which might take years, if not decades to emerge, we will assess whether any potential new regulations have reduced harm or increased injury.

The implications of this paralyzing uncertainty have been made more profound by the advent of new nicotine delivery devices such as electronic cigarettes. E-cigarettes are battery-powered vaporizers in which a heating element atomizes a solution of nicotine in glycerol or propylene glycol. Often flavors are added to increase palatability. Because e-cigarettes aerosolize a solution of nicotine by heating, many tobacco constituents are absent and the generation of combustion products is minimized. They produce no carbon monoxide, little tar, and only trace levels of carcinogenic nitrosamines, such as nicotine-derived nitrosamine and N-nitrosonornicotine.3 Bolstered by this favorable profile, and believing that much of the toxicity of conventional cigarettes is derived from combustion products and tobacco constituents other than nicotine, some argue that e-cigarettes are much less harmful than conventional cigarettes.4,5 They think that the use of e-cigarettes could meaningfully lessen the burden of smoking-related death, disease, and disability. Convinced of this view, they encourage current smokers to switch to e-cigarettes. The message seems to be sticking. The sales of e-cigarettes has skyrocketed. All major tobacco companies have started producing e-cigarettes. Vape shops have mushroomed all over the country, covering all market niches. Profits have doubled every year for the past 3 years, and the industry is expected to be worth $10 billion by 2017. A fringe phenomenon has become mainstream.

Reasons underlying the successes of the e-cigarette industry remain unclear. Users offer many reasons why they have taken to e-cigarettes. Some use e-cigarettes because they think that these devices are less harmful than conventional cigarettes, whereas others use them to circumvent clean air laws, to vape in places where smoking is prohibited or to prevent secondhand exposure to those near them. Many smokers use e-cigarettes to quit smoking. They think that e-cigarettes can help them wean-off conventional cigarettes. Weak data from surveys, personal testimony, and randomized trials6–8 are cited to support the notion that e-cigarettes are at least as effective as conventional nicotine replacement therapy and could help some individuals kick their smoking habit. E-cigarette manufacture implicitly, and often explicitly, promote this view, marketing their products as potential cessation devices.

Some view such developments with enthusiasm. Convinced of the favorable emission profiles of e-cigarettes, their wide public acceptance, and their potential as cessation devices, they think that widespread use of these devices might decisively banish the scourge of smoking from our society and ease the heavy toll of misery, disease, and death9,10 that cigarettes have extracted from those who succumb to their addictive attraction. They expect that adults and children would use e-cigarettes as a gateway out of smoking, not into it. They imagine a future in which combustible products are obsolete and those addicted to nicotine feed their habit with rather innocuous vaporizers, a future where the rates of heart disease, cancer, and chronic obstructive pulmonary disease have plummeted and even those addicted to nicotine live long, healthy lives.

Others are less persuaded by this utopian view. They point out that direct rigorous evidence showing that e-cigarettes are less harmful than conventional cigarettes is lacking and that better quality data are need to conclude that e-cigarettes are effective cessation devices. They worry that the e-cigarette emissions contain harmful levels of fine particles11 and toxic aldehydes12,13 that have been linked to a majority of the harmful noncancer effects of conventional cigarettes.14 They fear that acceptance of e-cigarettes might renormalize smoking, promote dual use, and increase nicotine dependence by enabling use in places where smoking is banned.15 They are alarmed by the rapid rise of e-cigarette use in youth, even in those who have not used a nicotine product before,16,17 and they are concerned that the use of a plethora of flavors and additives,18 which have not been tested for safety as inhaled chemicals, could lead to new diseases such as the popcorn lung19 or attract children and youth to a dangerous, lifelong addiction to nicotine. They do not think that nicotine is innocuous and cite extensive literature documenting that nicotine is a strong vasoactive drug, responsible for the variety of hemodynamic effects of smoking such as an increase in blood pressure and heart rate,20 and that it might be responsible for triggering acute cardiovascular events in smokers. They raise the possibility that decreased harm by reduced e-cigarette emissions may be offset by increased use. They point out that the dose–response relationship between smoking and cardiovascular mortality is nonlinear, in which most (80%) of the harm is incurred at low dose of exposure (<3 cigarettes per day)21; therefore, reduction in harmful or potentially harmful substances in e-cigarettes may not result in proportional harm reduction. Although proponents of e-cigarette dismiss the idea, opponents fear that e-cigarette use could act as a gateway to the use of other more harmful drugs. Most importantly, they are wary of Big Tobacco. They refuse to think that Big Tobacco is manufacturing e-cigarettes for altruistic purposes of reducing nicotine addiction and harm.14 Moving forward, they are looking back to years of lies, deception, and cover ups by the tobacco industry and their repeated attempts to deny that cigarettes are addictive and to develop safer products such as low-tar cigarettes that turned out to be no safer than previous products. They question the newly acquired harm reduction attitude of Big Tobacco when it continues to offer a cornucopia of child-friendly flavors familiar at preschoolers’ birthday parties.22

So, is there a path forward? Can opposing camps reconcile and support policies and regulation that would be widely accepted by the public? For now, this seems difficult. The field has become increasing polarized, and e-cigarettes have been the subject of many sharp, and sharply contested, debates among public health advocates. In the United Kingdom, Public Health England has declared that e-cigarettes are 95% safer than regular cigarettes.23 Some think that the promulgation is flawed24 and confusing25 because it replaces opinions with evidence and that it is deceptive because, by putting a specific number, it conveys a sense of accuracy and knowledge, which are currently lacking. Moreover, it assumes that 95% of the harmful effects of e-cigarettes are because of combustion products and that nicotine and residuals toxic compounds and particles, present in e-cigarette aerosols, contribute to <5% of the toxicity of conventional cigarettes, which is unlikely to be the case. Although it is understandable that this is one of the incidences in which we have to adopt a well-reasoned stance, even in the absence of relevant evidence, we cannot abandon our commitment to evidence-based policy making or offer opinions at odds with extant knowledge. Hence, for now, it might be more prudent to acknowledge ignorance, which has resulted from our failure to consider fully the complexities of the health effects of tobacco and tobacco-related disease.

As we wait for the relevant evidence to emerge, we have to find ways to regulate marketing, youth access, and labeling; to prohibit free sampling; and to set standards for contamination.26 Also, device characteristics should be regulated to minimize the risk of fires and explosions,14 and bottles containing nicotine should have child-proof packaging to prevent accidental swallowing or exposure. Importantly, companies should not be permitted to claim that their devices are cessation aids unless they present rigorous, convincing data supporting their claims.14,26 Such minimal regulations would ensure that the use of e-cigarettes does not result in unintended harm and that manufacturers in their enthusiasm to promote e-cigarette sales, do not compromise safety, overstep the boundaries of currently available evidence, or erode years of public health gains in denormalizing tobacco use. Going forward, we must re-evaluate the relationship between tobacco and disease; understand how tobacco products inflict injury; which ingredients, components, and constituents contribute to this risk; and which specific biomarkers can be followed to estimate harm and exposure. We have to resolve these issues, not only for e-cigarettes but also for other tobacco products such as hookah, cigars, cigarillos, and smokeless tobacco as well. We have to locate, with clarity, where e-cigarettes are within the current tobacco landscape, and we have to agree on larger, more profound questions regarding the social acceptance of nicotine addiction and its potential health effects. Whatever we choose to do, we have to proceed urgently, but with care, caution, and responsibility, because during the next decades, our actions could impact >1 billion lives.

Sources of Funding

Work in my laboratory is supported in part by the NIH grant HL120163 to the American Heart Association. The views expressed in this article do not necessarily reflect the views of the American Heart Association or the Food and Drug Administration.

Disclosures

None.

Footnotes

The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.

. The efficacy and short-term effects of electronic cigarettes as a method for smoking cessation: a systematic review and a meta-analysis.Int J Public Health. 2016;61:257–267. doi: 10.1007/s00038-016-0786-z.

; American Heart Association Advocacy Coordinating Committee, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Quality of Care and Outcomes Research. Electronic cigarettes: a policy statement from the American Heart Association.Circulation. 2014;130:1418–1436. doi: 10.1161/CIR.0000000000000107.